Pub Date : 2024-05-29DOI: 10.1101/2024.05.28.24308079
Steffen Flindt Nielsen, Camilla Lundgreen Duus, Niels Henrik Buus, Jesper Nørgaard Bech, Frank Holden Mose
Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute to this. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories.
{"title":"Renal and systemic hemodynamic effects of empagliflozin: Three randomized, double blind, placebo controlled cross-over trials","authors":"Steffen Flindt Nielsen, Camilla Lundgreen Duus, Niels Henrik Buus, Jesper Nørgaard Bech, Frank Holden Mose","doi":"10.1101/2024.05.28.24308079","DOIUrl":"https://doi.org/10.1101/2024.05.28.24308079","url":null,"abstract":"<strong>Background</strong> Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcomes in type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD). A decrease in renal blood flow (RBF) with attenuation of glomerular hyperfiltration may contribute to this. We examined renal and systemic hemodynamic effects of SGLT2i in relevant patient categories.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141189677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1101/2024.05.09.24307127
Saed Sayad, Mark Hiatt, Hazem Mustafa
Background Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, marked by inflammation, demyelination, and neurodegeneration. Diagnosis is complex due to overlapping symptoms with other neurological conditions, typically relying on clinical evaluation, neurological exams, and tests like magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Recent advances in technology, particularly single-cell analysis of blood and CSF leukocytes, hold promise for enhancing MS diagnosis by providing insights into immune cell involvement at a molecular level, potentially enabling more precise diagnostics and personalized treatments.
{"title":"Comparing Single-Cell Transcriptomes of Blood and Cerebrospinal Fluid Leukocytes in Multiple Sclerosis","authors":"Saed Sayad, Mark Hiatt, Hazem Mustafa","doi":"10.1101/2024.05.09.24307127","DOIUrl":"https://doi.org/10.1101/2024.05.09.24307127","url":null,"abstract":"<strong>Background</strong> Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, marked by inflammation, demyelination, and neurodegeneration. Diagnosis is complex due to overlapping symptoms with other neurological conditions, typically relying on clinical evaluation, neurological exams, and tests like magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Recent advances in technology, particularly single-cell analysis of blood and CSF leukocytes, hold promise for enhancing MS diagnosis by providing insights into immune cell involvement at a molecular level, potentially enabling more precise diagnostics and personalized treatments.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140941985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1101/2024.04.29.24306572
Anna Popova, Baiba Slisere, Karlis Racenis, Viktorija Kuzema, Roberts Karklins, Mikus Saulite, Janis Seilis, Anna Jana Saulite, Aiga Vasilvolfa, Kristine Vaivode, Dace Pjanova, Juta Kroica, Harijs Cernevskis, Aivars Lejnieks, Aivars Petersons, Kristine Oleinika
Background IgA nephropathy (IgAN) is characterised by the production of galactose-deficient IgA1 (Gd-IgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA-secretion remain unknown.
背景 IgA 肾病（IgAN）的特征是产生半乳糖缺乏性 IgA1（Gd-IgA1）抗体。作为致病抗体的来源，B 细胞是 IgAN 发病机制的核心，但 B 细胞活化途径以及 B 细胞分泌失调 IgA 的潜在来源仍不清楚。
{"title":"Enhanced differentiation of IgA+ class-switched CD27-CD21+ B cells in patients with IgA nephropathy","authors":"Anna Popova, Baiba Slisere, Karlis Racenis, Viktorija Kuzema, Roberts Karklins, Mikus Saulite, Janis Seilis, Anna Jana Saulite, Aiga Vasilvolfa, Kristine Vaivode, Dace Pjanova, Juta Kroica, Harijs Cernevskis, Aivars Lejnieks, Aivars Petersons, Kristine Oleinika","doi":"10.1101/2024.04.29.24306572","DOIUrl":"https://doi.org/10.1101/2024.04.29.24306572","url":null,"abstract":"<strong>Background</strong> IgA nephropathy (IgAN) is characterised by the production of galactose-deficient IgA1 (Gd-IgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA-secretion remain unknown.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1101/2024.04.15.24304270
Zaher A. Armaly, Yaacov Nitzan, Gil Chernin, Doron Aronson
Background Hemodialysis patients are susceptible to excess volume accumulation, particularly over the 2-day interval (long interdialytic gap), resulting in higher interdialytic weight gain (IDWG).
{"title":"Harnessing the Eccrine Sweat Glands for the Management of Interdialytic Weight Gain – A Pilot Study","authors":"Zaher A. Armaly, Yaacov Nitzan, Gil Chernin, Doron Aronson","doi":"10.1101/2024.04.15.24304270","DOIUrl":"https://doi.org/10.1101/2024.04.15.24304270","url":null,"abstract":"<strong>Background</strong> Hemodialysis patients are susceptible to excess volume accumulation, particularly over the 2-day interval (long interdialytic gap), resulting in higher interdialytic weight gain (IDWG).","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1101/2024.04.09.24305566
Marcello Tonelli, Natasha Wiebe
Background We did this study to develop and validate a risk score for new chronic kidney disease (CKD), focusing on predictors that are typically available in Canadian administrative health datasets.
{"title":"A simple risk score for chronic kidney disease using administrative data: A population-based cohort study","authors":"Marcello Tonelli, Natasha Wiebe","doi":"10.1101/2024.04.09.24305566","DOIUrl":"https://doi.org/10.1101/2024.04.09.24305566","url":null,"abstract":"<strong>Background</strong> We did this study to develop and validate a risk score for new chronic kidney disease (CKD), focusing on predictors that are typically available in Canadian administrative health datasets.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1101/2024.04.08.24305486
Alysha S. Thompson, Martina Gaggl, Nicola P. Bondonno, Amy Jennings, Joshua K. O’Neill, Claire Hill, Nena Karavasiloglou, Sabine Rohrmann, Aedín Cassidy, Tilman Kühn
Background Plant-rich dietary patterns may protect against negative health outcomes among individuals with chronic kidney disease (CKD), although aspects of plant-based diet quality have not been studied. This study aimed to examine associations between healthful and unhealthful plant-based dietary patterns with risk of mortality among CKD patients for the first time.
{"title":"Adherence to a healthful plant-based diet and risk of mortality among individuals with chronic kidney disease: A prospective cohort study","authors":"Alysha S. Thompson, Martina Gaggl, Nicola P. Bondonno, Amy Jennings, Joshua K. O’Neill, Claire Hill, Nena Karavasiloglou, Sabine Rohrmann, Aedín Cassidy, Tilman Kühn","doi":"10.1101/2024.04.08.24305486","DOIUrl":"https://doi.org/10.1101/2024.04.08.24305486","url":null,"abstract":"<strong>Background</strong> Plant-rich dietary patterns may protect against negative health outcomes among individuals with chronic kidney disease (CKD), although aspects of plant-based diet quality have not been studied. This study aimed to examine associations between healthful and unhealthful plant-based dietary patterns with risk of mortality among CKD patients for the first time.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.1101/2024.04.05.24304760
Takayasu Mori, Takuya Fujimaru, Chunyu Liu, Karynne Patterson, Kohei Yamamoto, Takefumi Suzuki, Motoko Chiga, Akinari Sekine, Yoshifumi Ubara, Danny E Miller, Miranda PG Zalusky, Shintaro Mandai, Fumiaki Ando, Yutaro Mori, Hiroaki Kikuchi, Koichiro Susa, University of Washington Center for Rare Disease Research, Jessica X. Chong, Michael J. Bamshad, Yue-Qiu Tan, Feng Zhang, Shinichi Uchida, Eisei Sohara
Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ∼80% of cases have a genetic explanation, while the genetic basis of sporadic cystic kidney disease in adults remains unclear in ∼30% of cases. This study aimed to identify novel genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. A next-generation sequencing panel analyzed known genes related to renal cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Three male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (CFAP47). CFAP47 was expressed in primary cilia of human renal tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation. This discovery of CFAP47 as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of CFAP47 in PKD.
{"title":"CFAP47 is a novel causative gene implicated in X-linked polycystic kidney disease","authors":"Takayasu Mori, Takuya Fujimaru, Chunyu Liu, Karynne Patterson, Kohei Yamamoto, Takefumi Suzuki, Motoko Chiga, Akinari Sekine, Yoshifumi Ubara, Danny E Miller, Miranda PG Zalusky, Shintaro Mandai, Fumiaki Ando, Yutaro Mori, Hiroaki Kikuchi, Koichiro Susa, University of Washington Center for Rare Disease Research, Jessica X. Chong, Michael J. Bamshad, Yue-Qiu Tan, Feng Zhang, Shinichi Uchida, Eisei Sohara","doi":"10.1101/2024.04.05.24304760","DOIUrl":"https://doi.org/10.1101/2024.04.05.24304760","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD) is a well-described condition in which ∼80% of cases have a genetic explanation, while the genetic basis of sporadic cystic kidney disease in adults remains unclear in ∼30% of cases. This study aimed to identify novel genes associated with polycystic kidney disease (PKD) in patients with sporadic cystic kidney disease in which a clear genetic change was not identified in established genes. A next-generation sequencing panel analyzed known genes related to renal cysts in 118 sporadic cases, followed by whole-genome sequencing on 47 unrelated individuals without identified candidate variants. Three male patients were found to have rare missense variants in the X-linked gene Cilia And Flagella Associated Protein 47 (<em>CFAP47</em>). CFAP47 was expressed in primary cilia of human renal tubules, and knockout mice exhibited vacuolation of tubular cells and tubular dilation, providing evidence that <em>CFAP47</em> is a causative gene involved in cyst formation. This discovery of <em>CFAP47</em> as a newly identified gene associated with PKD, displaying X-linked inheritance, emphasizes the need for further cases to understand the role of <em>CFAP47</em> in PKD.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29DOI: 10.1101/2024.03.28.24305010
Bernard Chan, Amanda Varghese, Sunil V Badve, Roberto Pecoits-Filho, Murilo Guedes, Clare Arnott, Rebecca Kozor, Emma O'Lone, Min Jun, Sradha Kotwal, Geoffrey A Block, Glenn M Chertow, Scott D Solomon, Muthiah Vaduganathan, Brendon L Neuen
Background and aims Heart failure and chronic kidney disease (CKD) are closely linked, with iron deficiency being highly prevalent in both conditions. Yet, major cardiovascular and nephrology guidelines offer contrasting recommendations on the use of iron. We evaluated the effects of iron versus usual care/placebo on clinical outcomes in patients with CKD. Methods We conducted a systematic review and meta-analysis of randomised trials of intravenous or oral iron in CKD (PROSPERO CRD42023453468). We searched Medline, Embase and the Cochrane Register from database inception until February 1, 2024 to identify eligible trials. We determined results overall and stratified by dialysis- and non-dialysis-requiring CKD using random effects models, with certainty of evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary composite endpoint was heart failure hospitalisation or cardiovascular death. Results We identified 45 trials that met our inclusion criteria. Compared to usual care/placebo, iron reduced the risk of the primary composite endpoint (1659 events; RR 0.84, 95% CI 0.75-0.94; moderate certainty) an effect consistent across dialysis and non-dialysis requiring CKD (P-heterogeneity=0.70). The effect on the primary endpoint appeared driven by both components of hospitalisation for heart failure (RR 0.77; 95% CI 0.61-0.96; moderate certainty) and cardiovascular death (RR 0.81; 95% CI 0.65-1.02; low certainty). The incidence of serious adverse events was lower for iron compared to usual care/placebo (RR 0.90, 95% CI 0.82-0.98; moderate certainty; P-heterogeneity=0.09). Conclusion Iron therapies may reduce the risk of heart failure or cardiovascular death in patients with CKD. Randomised trials evaluating effects of iron on clinical outcomes are needed, especially in non-dialysis CKD, with or without anaemia.
背景和目的心力衰竭和慢性肾脏病（CKD）密切相关，缺铁在这两种疾病中都非常普遍。然而，主要的心血管指南和肾脏指南对铁的使用提出了截然不同的建议。我们评估了铁剂与常规护理/安慰剂对 CKD 患者临床预后的影响。方法我们对 CKD 患者静脉注射或口服铁剂的随机试验进行了系统回顾和荟萃分析（PROSPERO CRD42023453468）。我们检索了 Medline、Embase 和 Cochrane 注册表，从数据库开始到 2024 年 2 月 1 日，以确定符合条件的试验。我们使用随机效应模型确定了总体结果，并按需要透析和不需要透析的 CKD 进行了分层，使用建议评估、发展和评价分级 (GRADE) 方法评估了证据的确定性。主要的复合终点是心力衰竭住院或心血管死亡。与常规护理/安慰剂相比，铁剂可降低主要复合终点的风险（1659 例；RR 0.84，95% CI 0.75-0.94；中度确定性），其效果在需要透析和不需要透析的 CKD 中一致（P-异质性=0.70）。对主要终点的影响似乎由心力衰竭住院（RR 0.77；95% CI 0.61-0.96；中等确定性）和心血管死亡（RR 0.81；95% CI 0.65-1.02；低确定性）两部分驱动。与常规护理/安慰剂相比，铁剂的严重不良事件发生率较低（RR 0.90，95% CI 0.82-0.98；中度确定性；P-异质性=0.09）。需要进行随机试验，评估铁剂对临床结果的影响，尤其是在非透析性 CKD 患者中，无论是否伴有贫血。
{"title":"Effects of iron on cardiovascular, kidney and safety outcomes in patients with chronic kidney disease: a systematic review and meta-analysis","authors":"Bernard Chan, Amanda Varghese, Sunil V Badve, Roberto Pecoits-Filho, Murilo Guedes, Clare Arnott, Rebecca Kozor, Emma O'Lone, Min Jun, Sradha Kotwal, Geoffrey A Block, Glenn M Chertow, Scott D Solomon, Muthiah Vaduganathan, Brendon L Neuen","doi":"10.1101/2024.03.28.24305010","DOIUrl":"https://doi.org/10.1101/2024.03.28.24305010","url":null,"abstract":"Background and aims\u0000Heart failure and chronic kidney disease (CKD) are closely linked, with iron deficiency being highly prevalent in both conditions. Yet, major cardiovascular and nephrology guidelines offer contrasting recommendations on the use of iron. We evaluated the effects of iron versus usual care/placebo on clinical outcomes in patients with CKD.\u0000Methods\u0000We conducted a systematic review and meta-analysis of randomised trials of intravenous or oral iron in CKD (PROSPERO CRD42023453468). We searched Medline, Embase and the Cochrane Register from database inception until February 1, 2024 to identify eligible trials. We determined results overall and stratified by dialysis- and non-dialysis-requiring CKD using random effects models, with certainty of evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary composite endpoint was heart failure hospitalisation or cardiovascular death.\u0000Results\u0000We identified 45 trials that met our inclusion criteria. Compared to usual care/placebo, iron reduced the risk of the primary composite endpoint (1659 events; RR 0.84, 95% CI 0.75-0.94; moderate certainty) an effect consistent across dialysis and non-dialysis requiring CKD (P-heterogeneity=0.70). The effect on the primary endpoint appeared driven by both components of hospitalisation for heart failure (RR 0.77; 95% CI 0.61-0.96; moderate certainty) and cardiovascular death (RR 0.81; 95% CI 0.65-1.02; low certainty). The incidence of serious adverse events was lower for iron compared to usual care/placebo (RR 0.90, 95% CI 0.82-0.98; moderate certainty; P-heterogeneity=0.09).\u0000Conclusion\u0000Iron therapies may reduce the risk of heart failure or cardiovascular death in patients with CKD. Randomised trials evaluating effects of iron on clinical outcomes are needed, especially in non-dialysis CKD, with or without anaemia.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140324441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26DOI: 10.1101/2024.03.24.24304607
Giulia Barbieri, Lucia Cazzoletti, Roberto Melotti, Essi Hantikainen, Rebecca Lundin, Laura Barin, Martin Goegele, Peter Riegler, Pietro Manuel Ferraro, Peter Paul Pramstaller, Giovanni Gambaro, Maria Elisabetta Zanolin, Cristian Pattaro
Introduction. Kidney diseases are a public health burden but, except for chronic kidney disease (CKD), they are poorly investigated in the general population. In light of inadequate survey tools for use in population studies, we developed a novel questionnaire to retrospectively assess the main kidney diseases, integrating it within the Cooperative Health Research In South Tyrol (CHRIS) study conducted between 2011 and 2018 in the Alpine district of Val Venosta/Vinschgau (Italy). Methods. The questionnaire covers general kidney diseases, reduced kidney function, and renal surgeries. It was applied to the cross-sectional assessment of self-reported kidney health among 11,684 adults, along with measures of fasting estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). By factor analysis we contextualized the questionnaire content with respect to biochemical measurements. CKD was defined according to KDIGO guidelines, self-reported diagnosis, and their combination. Prevalence estimates were calibrated to the general target population via relative sampling weights. Results. In this population sample (median age=45 years; median eGFR=98.4 mL/min/1.73 m2; median UACR=5.7 mg/g), 8.3% of participants reported at least one kidney disease. Population-representative prevalence of glomerulonephritis, pyelonephritis, and congenital kidney diseases was 1.0%, 3.0%, and 0.2%, respectively, with corresponding odds ratio for females versus males of 1.4 (95% confidence interval: 1.0, 2.0), 8.7 (6.2, 12.3), and 0.7 (0.3, 1.6), respectively. CKD prevalence was 8.6% when based on KDIGO criteria and 0.7% when self-reported, indicating that 95.3% of affected individuals were unaware of having CKD, with a similar figure of 92.9% in those reporting diabetes or hypertension. Overall, 15.8% of the population was affected by a kidney disease of any kind. Conclusion. In this Alpine population, CKD prevalence aligned with Western European estimates. Kidney health questionnaire implementation in population studies is feasible and valuable to assess CKD awareness, which we found to be dramatically low.
{"title":"Development and evaluation of a kidney health questionnaire and estimates of chronic kidney disease prevalence in the Cooperative Health Research In South Tyrol (CHRIS) study","authors":"Giulia Barbieri, Lucia Cazzoletti, Roberto Melotti, Essi Hantikainen, Rebecca Lundin, Laura Barin, Martin Goegele, Peter Riegler, Pietro Manuel Ferraro, Peter Paul Pramstaller, Giovanni Gambaro, Maria Elisabetta Zanolin, Cristian Pattaro","doi":"10.1101/2024.03.24.24304607","DOIUrl":"https://doi.org/10.1101/2024.03.24.24304607","url":null,"abstract":"Introduction. Kidney diseases are a public health burden but, except for chronic kidney disease (CKD), they are poorly investigated in the general population. In light of inadequate survey tools for use in population studies, we developed a novel questionnaire to retrospectively assess the main kidney diseases, integrating it within the Cooperative Health Research In South Tyrol (CHRIS) study conducted between 2011 and 2018 in the Alpine district of Val Venosta/Vinschgau (Italy).\u0000Methods. The questionnaire covers general kidney diseases, reduced kidney function, and renal surgeries. It was applied to the cross-sectional assessment of self-reported kidney health among 11,684 adults, along with measures of fasting estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). By factor analysis we contextualized the questionnaire content with respect to biochemical measurements. CKD was defined according to KDIGO guidelines, self-reported diagnosis, and their combination. Prevalence estimates were calibrated to the general target population via relative sampling weights.\u0000Results. In this population sample (median age=45 years; median eGFR=98.4 mL/min/1.73 m2; median UACR=5.7 mg/g), 8.3% of participants reported at least one kidney disease. Population-representative prevalence of glomerulonephritis, pyelonephritis, and congenital kidney diseases was 1.0%, 3.0%, and 0.2%, respectively, with corresponding odds ratio for females versus males of 1.4 (95% confidence interval: 1.0, 2.0), 8.7 (6.2, 12.3), and 0.7 (0.3, 1.6), respectively. CKD prevalence was 8.6% when based on KDIGO criteria and 0.7% when self-reported, indicating that 95.3% of affected individuals were unaware of having CKD, with a similar figure of 92.9% in those reporting diabetes or hypertension. Overall, 15.8% of the population was affected by a kidney disease of any kind. Conclusion. In this Alpine population, CKD prevalence aligned with Western European estimates. Kidney health questionnaire implementation in population studies is feasible and valuable to assess CKD awareness, which we found to be dramatically low.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140299059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-19DOI: 10.1101/2024.03.18.24304401
Nanditha Anandakrishnan, Zhengzi Yi, Zeguo Sun, Tong Liu, Jonathan Haydak, Sean Eddy, Pushkala Jayaraman, Stefanie Defronzo, Aparna Saha, Qian Sun, Yang Dai, Anthony Mendoza, Gohar Mosoyan, Huei Hsun Wen, Jennifer A Schaub, Jia Fu, Thomas Kehrer, Rajasree Menon, Edgar A Otto, Bradley Godfrey, Mayte Suarezfarinas, Sean Lefferts, Akosua Twumasi, Kristin Meliambro, Alexander Charney, Adolfo Garcia-Sastre, Kirk Campbell, Luca G Gusella, John He, Lisa Miorin, Girish Nadkarni, Juan P. Wisnivesky, Hong Li, Matthias Kretzler, Steve Coca, Lili Chan, Weijia Zhang, Evren U Azeloglu
COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.
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